铁死亡在肝纤维化中的双刃剑作用

敖逸云; 吴安琪; 王正根

doi:10.12449/JCH260428

铁死亡在肝纤维化中的双刃剑作用

DOI: 10.12449/JCH260428

敖逸云^{1, 2},
吴安琪^{3, 4},
王正根^{2, 3, 5, , ,}

1.
南华大学附属第七医院（湖南省荣军优抚医院）消化内科，长沙 410000
2.
南华大学附属第二医院消化内科，湖南衡阳 421001
3.
南华大学附属第二医院消化道肿瘤基础与临床药理研究湖南省重点实验室，湖南衡阳 421001
4.
南华大学附属第二医院临床研究中心，湖南衡阳 421001
5.
南华大学附属第二医院消化系统疾病研究所，湖南衡阳 421001

基金项目:

湖南省卫生健康委基金 (20201932);

湖南省重点实验室基金 (2023TP1014)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：敖逸云负责资料分析，撰写论文；吴安琪参与查阅文献，修改论文；王正根负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
王正根， wangzghd@qq.com （ORCID： 0009-0003-4936-5449）

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出版历程
- 收稿日期: 2026-01-07
- 录用日期: 2026-03-03
- 出版日期: 2026-04-25

Ferroptosis as a double-edged sword in liver fibrosis

Yiyun AO^{1, 2},
Anqi WU^{3, 4},
Zhenggen WANG^{2, 3, 5
, ,
,}

1.
Department of Gastroenterology，The Seventh Affiliated Hospital of University of South China （Hunan Provincial Veterans Administration Hospital），Changsha 410000，China
2.
Department of Gastroenterology，The Second Affiliated Hospital of University of South China，Hengyang，Hunan 421001，China
3.
Hunan Province Key Laboratory of Basic and Clinical Pharmacological Research on Gastrointestinal Tumors，The Second Affiliated Hospital of University of South China，Hengyang，Hunan 421001，China
4.
Clinical Research Center，The Second Affiliated Hospital of University of South China，Hengyang，Hunan 421001，China
5.
Institute of Digestive Diseases，The Second Affiliated Hospital of University of South China，Hengyang，Hunan 421001，China

Research funding:

Health Research Project of Hunan Provincial Health Commission (20201932);

The Foundation of Hunan Provincial Key Laboratory (2023TP1014)

More Information

Corresponding author: WANG Zhenggen， wangzghd@qq.com （ORCID： 0009-0003-4936-5449）

摘要

摘要: 铁死亡在肝纤维化中呈现明确的“双刃剑”作用，其效应严格取决于靶细胞类型。在肝细胞中，特定信号通路（如抑制谷胱甘肽过氧化物酶4）诱发的铁死亡是驱动肝损伤并启动纤维化的关键因素，死亡的肝细胞通过释放损伤相关分子模式激活肝星状细胞；相反，在活化的肝星状细胞中，铁死亡则成为促进肝纤维化逆转的治疗靶点，通过干预其独特的抗氧化防御机制可实现选择性清除。此外，铁死亡还通过调控巨噬细胞极化与细胞间通讯，影响肝纤维化微环境的动态平衡。基于上述机制，靶向铁死亡已成为一种极具前景的精准治疗策略，本文系统梳理相关研究进展，对其临床转化的核心挑战与发展方向进行了总结与展望。
- 肝纤维化 /
- 铁死亡 /
- 肝星状细胞 /
- 病理过程
Abstract: Ferroptosis exhibits a clear “double-edged sword” effect in liver fibrosis， with its impact strictly dependent on the type of target cells. In hepatocytes， ferroptosis induced by specific signaling pathways （such as glutathione peroxidase 4 inhibition） is a key factor for driving hepatic injury and initiating fibrogenesis， and dying hepatocytes activate hepatic stellate cells by releasing damage-associated molecules； on the contrary， in activated hepatic stellate cells， ferroptosis becomes a therapeutic target for promoting liver fibrosis regression， and selective elimination can be achieved by disrupting their distinctive antioxidant defense mechanisms. Moreover， ferroptosis modulates the dynamic balance of the fibrotic liver microenvironment by regulating macrophage polarization and intercellular communication. Based on the above mechanisms， targeting ferroptosis has emerged as a promising strategy for precise treatment. This article summarizes related research advances and discusses the major challenges and future directions for clinical translation.
- Hepatic Fibrosis /
- Ferroptosis /
- Hepatic Stellate Cells /
- Pathologic Processes

HTML全文

注： System Xc^-，胱氨酸/谷氨酸反向转运蛋白；Glu，谷氨酸；L-Cys，胱氨酸；Gly，甘氨酸；Cys，半胱氨酸；GCL，γ-谷氨酰半胱氨酸连接酶；GSS，谷胱甘肽合成酶；GSH，谷胱甘肽；GSSG，氧化型谷胱甘肽；GPX4，谷胱甘肽过氧化物酶4；PL-PUFA-OOH，磷脂过氧物；PL-PUFA-OH，磷脂醇；PUFA-OOH，多不饱和脂肪酸过氧化物；PL，磷脂；PUFA，多不饱和脂肪酸；ACSL4，长链脂酰辅酶A合成酶4；LC-CoA，长链脂酰辅酶A；LPCAT3，溶血卵磷脂酰基转移酶3；PE，磷脂酰乙醇胺；LOX，脂氧合酶；ROS，活性氧；TF，转铁蛋白；TFR1，转铁蛋白受体1；STEAP3，铁还原酶；DMT1，二价金属离子转运蛋白1；FPN，铁泵蛋白；POR，细胞色素P450氧化还原酶；CYB5R1，细胞色素b5还原酶1。

图 1 肝细胞诱发铁死亡机制

Figure 1. Mechanism of ferroptosis induction in hepatocytes

下载: 全尺寸图片幻灯片

注： HSC，肝星状细胞；DAMP，损伤相关分子模式；TNF-α，肿瘤坏死因子α；IL-1，白细胞介素1；IL-6，白细胞介素6；TGF-β，转化生长因子β；FRMD6-AS1，FRMD6反义链长非编码RNA1；MafG，肌肉腱膜纤维肉瘤癌基因同源蛋白G；lncRNA-TUG1，牛磺酸上调基因1；ACSL4，长链脂酰辅酶A合成酶4。

图 2 铁死亡在肝纤维化发生与发展中的细胞特异性调控网络

Figure 2. Cell-type-specific regulatory network of ferroptosis in the initiation and progression of liver fibrosis

下载: 全尺寸图片幻灯片

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